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Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation (IMPAKT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03076151
Recruitment Status : Completed
First Posted : March 10, 2017
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges

Tracking Information
First Submitted Date  ICMJE February 2, 2017
First Posted Date  ICMJE March 10, 2017
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE February 12, 2018
Actual Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2017)
Tacrolimus bayesian estimator performance [ Time Frame: Month 3 ]
The evaluation of Bayesian estimator performance will be based on its capacity to predict tacrolimus AUC (Area Under the Curve), expressed as the bias (%) between the predicted AUC with the PK model and the tacrolimus AUC calculated using the linear trapezoidal rule.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03076151 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2017)
Tacrolimus concentrations predicted by the PK model using a limited sample strategy [ Time Frame: Month 3 ]
The evaluation of the Bayesian estimator performance will be based on its capacity to predict, using a limited number of samples collected during the early phase post-dose, observed tacrolimus AUC0-12h measured using the non-compartmental trapezoidal method with all the time points
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
Official Title  ICMJE Interventional Multicentre Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
Brief Summary

Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Adoport® is an immediate-release formulation of tacrolimus, to be administered twice daily. Because of a narrow therapeutic window and a better correlation between pre-dose level and effects than between dose and effect, therapeutic drug monitoring (TDM) based on trough whole blood tacrolimus concentrations is recommended for Adoport®. TDM helps to minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).

As reported in a consensus document from a consortium of European experts on tacrolimus TDM, the interdose area-under-the curve (AUC0-12h) is expected to be the best marker of tacrolimus exposure. However, tacrolimus monitoring based on full AUC0-12h is difficult to set up in routine, due to clinical constraints and the necessity of multiple samples. Calculation of the AUC0-12h using Bayesian estimation and a limited sampling strategy, i.e. a few blood samples collected during the early phase post-dose would represent an elegant solution, as already done for other tacrolimus formulations.

Furthermore, the pharmacokinetics (PK) of tacrolimus is influenced by a single nucleotide polymorphism within intron 3 of cytochrome P450 3A5 (CYP3A5). Patients who carry at least one CYP3A5*1 allele are considered to be CYP3A5 expressors (about 12% of the Caucasian population, Hapmap project) and thus require a 1.5 to 2-fold higher starting dose than CYP3A5*3/*3 carriers to reach the predefined target exposure early after transplantation. Although this polymorphism showed no impact on the performance of the Bayesian estimators previously developed for other tacrolimus formulation, the patient status for CYP3A5*3 will be considered in this pharmacokinetic study as a potential covariate in, or confounding factor of, the PK model. Specifically, owing to a 12% frequency in the White European population, about 4 patients carriers of the CYP3A5*1 allele are expected in this study; the performance of the PK model and Bayesian estimator developed will be specifically evaluated in this subgroup.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Transplantation
  • Kidney
  • Pharmacokinetic
Intervention  ICMJE Drug: Tacrolimus monohydrate (ADOPORT®)
Pharmacokinetic of Tracrolimus (ADOPORT®) on 9 blood sampling by kinetics on 4 kinetics
Study Arms  ICMJE Experimental: Tacrolimus monohydrate (ADOPORT®)
patients with de novo Kidney Transplantation under Tacrolimus (ADOPORT®) treatment.
Intervention: Drug: Tacrolimus monohydrate (ADOPORT®)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject's written informed consent of the study
  2. Male and female (>= 18 years)
  3. Recipients of a first kidney allograft
  4. Patients transplanted for less than 7 days at enrolment
  5. Patients affiliated to a social security system

Exclusion Criteria:

  1. Patients presenting any contraindication to tacrolimus according to the summary of product characteristics of Adoport®
  2. Patient presenting anti-HLA antibodies against the graft in pre-transplantation (DSA)
  3. Recipients of any transplanted organ other than the kidney
  4. Pregnant (positive BHCG test) or lactating women
  5. Women without any method of contraception, except for women with no childbearing potential (according to the guidelines of the working group, Clinical Trial Facilitation Group, related to contraception and pregnancy test in clinical trials)
  6. Patients participating in any other interventional clinical study at inclusion as well as during the whole course of the current study
  7. Patient under judicial protection
  8. Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03076151
Other Study ID Numbers  ICMJE I16009 (IMPAKT)
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Limoges
Study Sponsor  ICMJE University Hospital, Limoges
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pierre Marquet, MD University Hospital, Limoges
PRS Account University Hospital, Limoges
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP